Epithelium is the tissue that covers and lines the free surfaces of the body, and includes cells of the skin and sensory organs, as well as the specialized cells lining the blood vessels, gastrointestinal tract, air passages, ducts of the kidneys and endocrine organs. Epithelial cells maintain many diverse and essential cellular functions, including synthesizing and secreting proteins and other products, providing barriers, and proliferating to replace constantly eroded surface epithelia. Carcinomas, which are cancers derived from epithelial cells, account for the majority of malignant neoplasias, including most cancers of the breast, lung, colon, prostate, ovary, and pancreas.
The so-called DF3 gene encodes a high molecular weight glycoprotein which is aberrantly expressed by malignant human epithelia of various types. The DF3 glycoprotein is a member of a family of related carcinoma-associated antigens with core proteins ranging from 160 to 230 kD (Abe et al., J. Immunol. 139:257-261, 1987; Abe et al., Cancer Res. 49:2834-2839, 1989). This antigen is expressed on the apical borders of secretory mammary epithelium and at high levels in the cytosol of less differentiated malignant cells (Kufe et al., Hybridoma 3:223-232, 1984). DF3 antigen expression correlates with the degree of breast tumor differentiation (Lundy et al., Breast Cancer Res. Treat. 5:269-276,. 1985). Moreover, the detection of this antigen in human milk (Abe et al., Cancer Res. 44:4574-4577, 1984) has suggested that its expression represents a differentiated function of normal mammary cells.
Previous studies have demonstrated that the DF3 gene is highly over-expressed in human breast carcinomas and that expression of this gene is regulated at the transcriptional level (Kufe et al., Hybridoma 3:223-232, 1984; Abe et al., J. Cell. Physiol. 143:226-231, 1990).